胰十二指腸切除術后胰瘺的預防

吳傳有，劉長安，李生偉

(重慶醫科大學附屬第二醫院，重慶 400010)

胰十二指腸切除術由德國外科醫生Kausch在1909年首次實施[1]。Whipple等[2]于1935年報告3例胰十二指腸切除病案之后，胰十二指腸切除術就成為壺腹部腫瘤外科治療的選擇方式。而今，胰十二指腸切除術已經作為胰頭癌和壺腹周圍癌治療的標準手術方式。隨著手術技術的改進和術后管理的提高，已經使胰腺切除術后死亡率減少到5%以下，然而術后并發癥的發生率卻改變很小，仍然在30%～40%范圍[3-4]。術后胰瘺、腹腔出血、腹腔膿腫形成以及胃排空障礙等并發癥時有報道。術后胰瘺依然是胰十二指腸切除術后最常見、最嚴重的并發癥[5]，其發生率從2%～40%不等[5-6]。而這些并發癥的發生往往需要藥物或再次手術干預，以致延長住院時間，增加住院費用，甚至導致患者死亡。胰十二指腸切除術后胰瘺的風險因素包括一般因素(年齡[7]、性別[8]、黃疸指數[9]、營養狀況)、疾病因素(胰腺病理學、胰腺質地[10-12]、胰管擴張程度[13-14]、胰液輸出量)和手術因素(手術時間、切除類型、吻合技術/方式[15-16]、術中出血量)。此外,外科醫生的經驗已經被證明是與胰腺吻合口瘺有關的因素(如消化道重建方式、胰管支撐引流與否),預防性應用生長抑素也與胰瘺相關[17]。本文從胰十二指腸切除術后消化道重建、胰管支撐引流等方面為術后胰瘺的預防作一綜述。

1 消化道重建

1.1 胰胃吻合與胰腸吻合 胰十二指腸切除術后消化道重建與術后并發癥的發生率、死亡率以及患者的生活質量有著密切的關系。目前主要有兩種方式來完成胰十二指腸切除術后消化道重建。自1941年Hun和他的同事第一次報道胰腸套入式吻合術后，胰腸吻合就成為胰十二指腸切除術后消化道重建的主要手術方式；Waugh等[18]于1946年第一次報道了胰胃吻合術。Oida等[19]認為胃腸吻合有3個優點：①胃壁厚且血流豐富；②胰液的出口靠近胃的背側；③胃里面沒有腸激酶，胰液不易被激活。McKay等[20]認為胰胃吻合術后胰瘺的發生，以及并發癥的發生，總的死亡率明顯比胰腸吻合術后低。Topal等[21]通過對胰胃吻合與胰腸吻合的多中心隨機對照研究顯示：胰胃吻合能夠降低術后胰瘺的發生，但不能降低術后總的并發癥，且在胰胃吻合術后一旦發生胰瘺，將明顯增加患者的死亡風險及延長住院時間。Watanabe等[22]通過對81個中心、3 109例胰十二指腸切除術后病人的分析認為：胰胃吻合與胰腸吻合術后吻合口瘺的發生率(胰胃吻合11.0%，胰腸吻合13.3%)、腹腔內出血、腹腔膿腫形成、總的死亡率沒有明顯差別。He等[23]通過對1966—2011年胰胃吻合與胰腸吻合的隨機對照研究和臨床觀察研究的數據分析顯示，尚沒有足夠的證據證明胰胃吻合比胰腸吻合更安全，胰胃吻合與胰腸吻合術后總的死亡率相近。比起胰腸吻合，胰胃吻合可能減少術后胰瘺的發生和腹腔膿腫的形成，但卻增加術后腹腔出血的風險。Daisuke等[24]最近研究認為：胰胃吻合與胰腸吻合術后胰瘺發生無明顯不同，甚至在胰腺質地較軟的患者來說也是如此。

1.2 幾種常用的胰腸吻合 幾種常見的胰腺空腸吻合術包括：套入式胰腺空腸端端吻合、胰管空腸黏膜端端吻合、胰腺空腸端側吻合、胰管空腸黏膜端側吻合、胰管栓塞結扎法、捆綁式胰腸吻合術。胰管空腸黏膜吻合術由Cattle于1943年第一次使用，它允許胰管與空腸黏膜直接接觸，防止胰液與胰腺殘端直接接觸，促進黏膜愈合，保護嵌入空腸黏膜下吻合口，所以胰管空腸黏膜吻合理論上能夠防止術后胰瘺的發生。Poon等[25]發現胰管空腸黏膜吻合是一種安全的吻合方式。Marcus等[26]發現胰管空腸吻合用于胰腺質地較硬、胰管擴張的低危患者，術后胰瘺的發生率低；而端端吻合用于胰腺質地較軟、胰管不擴張的高危患者較安全。胰管栓塞結扎術因為廢除胰腺的外分泌功能，且術后胰瘺發生率也很高而不常用[27]。捆綁式胰腸吻合近來常被報道[28-31]。Hashimoto等[31]對傳統胰腸吻合與捆綁式胰腸吻合系統性分析認為：胰胃吻合與胰腸吻合術后胰瘺發生無明顯不同，甚至在胰腺質地較軟的患者來說也是如此。

2 胰管支撐引流

一些研究[32-34]認為胰十二指腸切除術后暫時性的胰管支撐引流能減少術后胰瘺的發生。Poon等[32]通過對120例胰腸吻合術后胰管支撐外引流與不引流的研究認為：胰管支撐外引流組術后胰瘺的發生率明顯低于非引流組(6.7%比20%，P=0.032)，且引流組的住院時間明顯短于非引流組(平均17 d比23 d，P=0.039)，但總的術后并發癥的發生率(31.7%比38.3%，P=0.444)和死亡率(1.7%比5%，P=0.309)沒有明顯的差別。Pessaux等[34]認為胰管支撐外引流可減少術后胰瘺的發生，尤其適用于那些胰腺質地較軟、胰管無明顯擴張的胰十二指腸切除。Winter等[35]通過對234例接受胰十二指腸切除、胰腸吻合、胰管支撐內引流與非引流的前瞻性隨機對照研究顯示：胰管支撐內引流組對比非引流組在預防胰瘺方面無明顯優勢，而且對于那些胰腺質地較軟、胰管無明顯擴張的患者來說，胰管支撐內引流增加術后胰瘺的發生率(21.0%比10.7%，P=0.13)。Tani等[36]研究認為胰十二指腸切除術后胰管支撐內引流與外引流比較，術后胰瘺的發生率無明顯差別，引流方式也不受胰腺質地影響，且簡化了術后管理，縮短住院時間。Zhou等[37]對胰十二指腸切除術胰管支撐內/外引流與不引流的Meta分析認為：胰管支撐外引流能減少術后胰瘺的發生，而胰管支撐內引流則不能減少胰瘺的發生，尤其是對胰腺質地較軟，胰管無明顯擴張的患者；最近的研究還認為，胰管支撐內引流不但不能減少術后胰瘺的發生，而且還有可能增加軟胰術后胰瘺的發生。

3 其他方式

此外，一些文獻已經報道了用大網膜、鐮狀韌帶包裹吻合口亦可有效地預防術后胰瘺的發生[38-39]，但是因為胰液中脂肪酶的作用，若發生胰瘺，則易形成腹腔膿腫。生長抑素及其類似物可以抑制胰腺的內分泌和外分泌，從而降低術后胰瘺的發生[40]。

4 結 論

總結胰十二指腸切除術后消化道重建的各種手術方式及術后的管理，我們認為：胰胃吻合與胰腸吻合術后胰瘺發生無明顯不同，兩種重建消化道方式各有利弊；文獻報道和外科醫生習慣更傾向于選擇胰腸吻合行胰十二指腸切除術后消化道重建；胰管空腸黏膜端側吻合，胰管支撐外引流能減輕胰液對吻合口的腐蝕，防止吻合口的梗阻，明顯降低術后胰瘺的發生率；用大網膜行胰腸吻合口包裹，術后常規使用生長抑素抑制胰腺分泌功能等，均能降低術后胰瘺及并發癥的發生率，我們推薦使用。

參考文獻：

[1]Abu Hilal M,Malik HZ,Hamilton-Burke W,et al.Modified Cattell’s pancreaticojejunostomy,buttressing for soft pancreases and an isolated biliopancreatic loop are safety measurements that improve outcome after pancreaticoduodenectomy: a pilot study[J].HPB (Oxford),2009,11(2):154-160.

[2]Whipple AO,Parsons WB,Mullins CR.Treatment of carcinoma of the ampulla of vater[J].Ann Surg,1935,102(4):763-779.

[3]Benzoni E, Saccomano E, Zompicchiatti A, et al.The role of pancreatic leakage on rising of postoperative complications following pancreatic surgery[J].J Surg Res, 2008,149(2):272-277.

[4]Hashimoto D,Takamori H,Sakamoto Y,et al.Is estimation of physiologic ability and surgical stress (E-PASS) able to predict operative morbidity after pancreaticoduodenectomy[J].J Hepatobiliary Pancreat Surg,2010,17(2):132-138.

[5]Bassi C,Dervenis C,Butturini G,et al.Postoperative pancreatic fistula: an international study group (ISGPF) definition[J].Surgery,2005,138(1):8-13.

[6]Butturini G,Daskalaki D,Molinari E,et al.Pancreatic fistula: definition and current problems[J].J Hepatobiliary Pancreat Surg,2008,15(3):247-251.

[7]Matsusue S,Takeda H,Nakamura Y,et al.A prospective analysis of the factors influencing pancreaticojejunostomy performed using a single method, in 100 consecutive pancreaticoduodenectomies [J].Surg Today,1998,28(7):719-726.

[8]Montorsi M,Zago M,Mosca F,et al.Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomizedclinical trial[J].Surgery,1995,117(1):26-31.

[9]Yeh TS,Jan YY,Jeng LB,et al.Pancreaticojejunal anastomotic leak after pancreaticoduodenectomy-multivariate analysis of perioperative risk factors[J].J Surg Res,1997,67(2): 119-125.

[10]Lin JW,Cameron JL,Yeo CJ,et al.Risk factors and outcomes in post pancreaticoduodenectomy pancreatico cutaneous fistula [J].J Gastointest Surg, 2004,8(8):951-959.

[11]Yang YM,Tian XD,Zhuang Y,et al.Risk factors of pancreatic leakage after pancreaticoduodenectomy[J].World J Gastroenterol,2005,11(16):2456-2461.

[12]Hosotani R,Doi R,Imamura M.Duct-to-mucosa pancreaticojejunostomy reduces the risk of pancreatic leakage after pancreatoduodenectomy [J].World J Surg,2002,26(1): 99-104

[13]Choe YM,Lee KY,Oh CA,et al.Riskfactorsaffecting pancreatic fistulas after pancreaticoduodenectomy[J].World J Gastroenterol,2008, 14(45):6970-6974.

[14]Satoi S,Toyokawa H,Yanagimoto H,et al.A new guideline to reducepostoperative morbidity after pancreaticoduodenectomy[J].Pancreas,2008,37(2):128-133.

[15]Hasegawa K,Kokudo N,Sano K,et al.Two-stage pancreato-jejunostomy in pancreaticoduodenectomy: a retrospective analysis of short-term results[J].Am J Surg,2008,196(1):3-10.

[16]Sugiyama M,Suzuki Y,Abe N,et al.Pancreatic duct holder forfacilitating duct-to-mucosa pancreatojejunostomy after pancreatoduodenectomy[J].Am J Surg, 2009,197(1):18-20.

[17]Yang YM,Tian XD,Zhuang Y,et al.Risk factors of pancreatic leakage after pancreaticoduodenectomy[J].World J Gastroenerol,2005,11(16):2456-2461.

[18]Waugh JM,Clagett OT. Resection of the duodenum and head of the pancreas for carcinoma;an analysis of thirty cases[J].Surgery,1946,20(1):224-232.

[19]Oida T,Mimatsu K,Kawasaki A,et al.Vertical stomach reconstruction with pancreaticogastrostomy after modified subtotal-stomach-preserving pancreaticoduodenectomyfor preventing delayed gastric emptying.Hepatogastroenterology,2009,56(90):565-567.

[20]McKay A,Mackenzie S,Sutherland FR,et al.Meta-analysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy[J].Br J Surg,2006,93(8):929-936.

[21]Topal B, Fieuws A, Aerts R,et al.Pancreaticojejunostomy versus pancreatico gastrostomyreconstruction after pancreatico-duodenectomy for pancreatic or periampullarytumours:a multicentrerandomised trial[J].Lancet Oncol,2013,14(7): 655-662.

[22]Watanabe M,Usui S,Kajiwara H,et al.Current pancreatog-astrointestinal anastomotic methods: results of a Japanese survey of 3109 patients[J].J Hepatobiliary Pancreat Surg,2004,11(1):25-33.

[23]He TY,Zhao Y,Chen QL,et al.Pancreaticojejunostomy versus Pancreaticogastrostomy after Pancreaticoduodenectomy:A Systematic Review and Meta-Analysis[J].Dig Surg,2013,30(1):56-69.

[24]Daisuke H， Akira C，Masaki O， et al. Pancreaticodigestive anastomosis and the postoperative management strategies to prevent postoperative pancreatic fistula formation after pancreaticoduodenectomy[J].Surgery Today,2013,DOI10.1007/s00595-013-0662-x.

[25]Poon RT,Lo SH,Fong D,et al.Prevention of pancreatic anastomotic leakage after pancreaticoduodenectomy [J].Am J Surg,2002,183(1):42-52.

[26] Marcus SG,Cohen H,Ranson JH.Optimal management of the pancreatic remnant after pancreaticoduodenectomy[J].Ann Surg,1995,221(6): 635-645.

[27]Marczell AP,Stierer M.Partial pancreaticoduodenectomy (Whipple procedure) for pancreatic malignancy: occlusion of a non-anastomosed pancreatic stump with fibrin sealant[J].HPB Surg,1992,5(4): 251-259.

[28]Buc E,Flamein R,Golffier C,et al.Peng’s binding pancreaticojejunostomy after pancreaticoduodenectomy:a French prospective study[J].J Gastrointest Surg,2010,14(4):705-710.

[29]Nordback I,Raty S,Laukkarinen J,et al.A novel radiopaque biodegradable stent for pancreatobiliary applications the first human phase I trial in the pancreas[J]. Pancreatology,2012,12(3):264-271.

[30]Hashimoto D, Hirota M,Yagi Y,et al.End-to-side pancreaticojejunostomy without stitches on the pancreatic stump[J].Surg Today,2013, doi:10.1007/s00595-012-0371-x.

[31]Hashimoto D,Hirota M,Chikamoto A,et al.Short term outcome of new end-to-side inserting pancreatico-jejunostomy without stitches on the pancreatic cut end[M].Hepatogastroenterology,2013 (in press).

[32]Poon RT,Fan ST,Lo CM,et al.External drainage of pancreatic duct with a stent to reduce leakage rate of pancreaticoje-junostomy after pancreaticoduodenectomy:a prospective randomized trial[J].Ann Surg,2007,246(3):425-435.

[33]Kamoda Y,Fujino Y,Matsumoto I,et al.Usefulness of performing a pancreaticojejunostomy with an internal stent after pancreatoduodenectomy[J].Surg Today,2008,38(6):524-528.

[34]Pessaux P,Sauvanet A,Mariette C,et al.External pancreatic duct stent decreases fistula rate after pancreaticoduo-denectomy:prospective multicenter randomized trial[J].Ann Surg,2011,253(5):879-885.

[35]Winter JM,Cameron JL,Campbell KA,et al.Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial[J].J Gastrointest Surg,2006,10(9):1280-1290.

[36]Tani M,Kawai M,Hirono S,et al.A prospective randomized controlled trial of internal versus external drainage with pancreaticojejunostomy for pancreaticoduodenectomy[J].Am J Surg,2010,199(6):759-764.

[37]Zhou Y,Zhou QB,Li ZH,et al.Internal pancreatic duct stent does not decrease pancreatic fistula rate after pancreatic resection:a meta-analysis[J].Am J Surg,2013,205(16):718-725.

[38]Abe N,Sugiyama M,Suzuki Y,et al.Falciform ligament in pancreatoduodenectomy for protectionof skeletonized and divided vessels[J].J Hepatobiliary Pancreat Surg,2009,16(2):184-188.

[39]Kurosaki I,Hatakeyama K.Omental wrapping of skeletonizedmajor vessels after pancreaticoduodenectomy[J].Int Surg,2004,89(2):90-94.

[40]Gurusamy KS,Koti R,Fusai G,et al.Somatostatin analogues for pancreaticsurgery[J].Cochrane Database Syst Rev,2013,30(40):CD008370.